DPP-4

Dipeptidyl peptidase-4 (DPP-4), also known as CD26, is a membrane-associated and soluble serine exopeptidase that cleaves peptides containing alanine or proline at the penultimate N-terminal position, thereby regulating the biological activity of multiple peptide hormones and signaling molecules^[1][2]. Mechanistically, DPP-4 is a key regulator of the incretin pathway because it rapidly degrades the active forms of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), generating truncated products with markedly reduced biological activity and limiting incretin-mediated glucose control^[3][4][5]. Through this enzymatic process, DPP-4 influences insulin secretion, glucagon regulation, and systemic glucose homeostasis, making it a central component of metabolic signaling networks relevant to type 2 diabetes mellitus (T2DM) and related metabolic disorders^[4][6][7]. In disease contexts, elevated DPP-4 activity has been associated with insulin resistance, inflammation, obesity, and T2DM, supporting its use as a mechanistic target and biomarker in metabolic research models^[2]. Compared with related members of the dipeptidyl peptidase family, DPP-4 is distinguished by its well-characterized role in incretin degradation and its dual function as both an enzymatic regulator and a cell-surface signaling molecule, which contributes to its broad physiological relevance^[1][2]. For experimental applications, selective DPP-4 inhibitors are widely used to prolong endogenous GLP-1 and GIP activity, enhance glucose-dependent insulin secretion, and improve glycemic control, providing robust pharmacological tools for investigating incretin biology and metabolic disease mechanisms^[6][7][8].